Comer A M, Perry C M, Figgitt D P
Adis International Limited, Auckland, New Zealand.
Paediatr Drugs. 2001;3(1):61-79. doi: 10.2165/00128072-200103010-00005.
Apnoea of prematurity is a common condition in neonates born at less than 37 weeks' gestational age; it affects approximately 90% of premature neonates weighing under 1000 g at birth, and 25% of infants with a birthweight of less than 2500 g. Caffeine, a methylxanthine which occurs naturally in many plants, has been used for over 20 years to treat apnoea of prematurity. In a recent double-blind, placebo-controlled trial, apnoea was eliminated or reduced by at least 50% in significantly more neonates receiving caffeine citrate as first-line treatment than those receiving placebo. In a nonblind trial, caffeine citrate was more effective at reducing apnoeic episodes when compared with neonates receiving no treatment. Caffeine as first-line treatment demonstrated similar efficacy to theophylline or aminophylline (theophylline ethylenediamine) in 4 small randomised studies. Caffeine citrate was generally well tolerated in short term clinical trials, with very few adverse events reported. Caffeine was associated with fewer adverse events than theophylline in randomised trials. No differences in the incidence of individual adverse events were reported between caffeine citrate and placebo in a double-blind, randomised trial. Long term tolerability data are not yet available.
Caffeine citrate was generally well tolerated by neonates in clinical trials and it decreased the incidence of apnoea of prematurity compared with placebo. It has demonstrated similar efficacy to theophylline, but is generally better tolerated and has a wider therapeutic index. Caffeine citrate should, therefore, be considered the drug of choice when pharmacological treatment of apnoea of prematurity is required.
早产窒息是孕龄小于37周出生的新生儿的常见病症;它影响约90%出生体重低于1000g的早产新生儿,以及25%出生体重低于2500g的婴儿。咖啡因是一种在许多植物中天然存在的甲基黄嘌呤,已用于治疗早产窒息20多年。在最近一项双盲、安慰剂对照试验中,与接受安慰剂的新生儿相比,接受枸橼酸咖啡因作为一线治疗的新生儿中,窒息消除或减少至少50%的比例显著更高。在一项非盲试验中,与未接受治疗的新生儿相比,枸橼酸咖啡因在减少呼吸暂停发作方面更有效。在4项小型随机研究中,咖啡因作为一线治疗显示出与茶碱或氨茶碱(氨茶碱乙二胺)相似的疗效。在短期临床试验中,枸橼酸咖啡因一般耐受性良好,报告的不良事件极少。在随机试验中,咖啡因相关的不良事件比茶碱少。在一项双盲、随机试验中,未报告枸橼酸咖啡因与安慰剂之间个体不良事件发生率的差异。长期耐受性数据尚不可用。
在临床试验中,新生儿对枸橼酸咖啡因一般耐受性良好,与安慰剂相比,它降低了早产窒息的发生率。它已显示出与茶碱相似的疗效,但一般耐受性更好,治疗指数更宽。因此,在需要对早产窒息进行药物治疗时,枸橼酸咖啡因应被视为首选药物。